非综合征型聋家系SLC26A4基因复合杂合突变

Compound heterozygous mutation of SLC26A4 genein a family with nonsyndromic deafness

目的 研究1例前庭导水管扩大患者的遗传方式和基因突变位点。方法 以1例临床诊断为前庭导水管扩大的患者及其健康的父母为研究对象,采集其静脉血,使用全外显子测序技术检测先证者的遗传序列,进行生物信息学分析,锁定该患者可能的致病基因及突变位点,并进一步采用Sanger测序法对其父母进行相关突变位点验证,最终确定该患者的致病基因;通过单核苷酸多态性位点分析、氨基酸保守性分析及氨基酸序列分析等手段,分析复合杂合突变的致病机制,绘制突变的遗传系谱。结果 该患者致病突变定位于7q31的SLC26A4基因,由c.919-2A>G、c.1746del G以及c.563T>C 3个位点组成的复合杂合突变。SLC26A4基因的c.919-2A>G突变遗传自其听力正常的父亲,而SLC26A4基因的c.1746del G和c.563T>C突变均遗传自其听力正常的母亲。结论 先证者携带的SLC26A4基因的3个突变位点均是明确的与听力损伤相关的隐性疾病突变位点。因此,推测SLC26A4基因的上述3个突变以某种复合杂合的形式导致受检者患病。

Objective To investigate the genetic pattern and mutation sites of a patient with enlarged vestibular aqueduct(EVA).Methods The venous blood samples of a patient clinically diagnosed with EVA and her healthy parents were collected,and the genetic sequence of the proband was detected by whole exon sequencing technology for bioinformatics analysis.The possible pathogenic genes and mutation sites of this patient were identified,and the relevant mutation sites of the parents were further verified by Sanger sequencing method.The pathogenic gene of the patient was finally determined.By means of single nucleotide polymorphism site analysis,amino acid conserved analysis and amino acid sequence analysis,the pathogenic mechanism of compound heterozygous mutations was analyzed,and the genetic pedigree of mutations was drawn.Results The pathogenic mutation in this patient was located in SLC26A4 gene of 7q31,with a compound heterozygous mutation consisting of c.919-2A>G,c.1746del G and c.563T>C.The c.919-2A>G mutation of SLC26A4 was inherited from her healthy father,while the c.1746del G and c.563T>C mutations of SLC26A4 were both inherited from her healthy mother.Conclusion The three mutation sites of SLC26A4 gene carried by the proband were all clear recessive disease mutation sites associated with hearing impairment.Therefore,the above three mutations in SLC26A4 gene are presumed to cause disease in subjects in some form of compound heterozygosity.